Brief Summary
This study is to determine whether JX-594 (Pexa-Vec) plus best supportive care is more effective in improving survival than best supportive care in patients with advanced Hepatocellular Carcinoma (HCC) who have failed sorafenib.
Brief Title
A Phase 2b Study of Modified Vaccinia Virus to Treat Patients Advanced Liver Cancer Who Failed Sorafenib
Detailed Description
This Phase 2b, open-label, randomized, multi-center study is designed to evaluate the efficacy and safety of JX-594 (Pexa-Vec) in patients with advanced hepatocellular carcinoma (HCC) who have previously failed sorafenib treatment. Eligible patients are randomly assigned in a 2:1 ratio to receive either the experimental therapy (JX-594 plus Best Supportive Care \[BSC\]) or the control therapy (BSC alone).
Patients assigned to the experimental arm receive an initial intravenous (IV) infusion of JX-594 on Day 1. This is followed by intratumoral (IT) injections of JX-594 directly into viable liver tumors under imaging guidance on Day 8, Day 22, and Weeks 6, 12, and 18. These patients will also receive BSC, but active anti-cancer treatments are strictly prohibited. In contrast, patients in the control arm receive only Best Supportive Care (e.g., hydration, nutrition, pain management) at the treating physician's discretion without any study drug injections. Experimental or active anti-cancer therapies are not permitted in the control arm.
The primary objective of this study is to compare the Overall Survival (OS) between the two treatment arms. Secondary objectives include evaluating Time-to-Tumor Progression (TTP) and objective response rate based on mRECIST criteria for HCC. The study also evaluates Time-to-Symptomatic Progression (TSP), which is defined by changes in the FACT Hepatobiliary Symptom Index (FHSI-8) questionnaire and ECOG performance status. Additionally, the study assesses changes in Quality of Life (QoL) measured by EORTC and FACT-Hep questionnaires. Finally, overall safety and tolerability are closely monitored through the incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) graded according to NCI CTCAE v4.03, along with clinical laboratory evaluations.
Patients assigned to the experimental arm receive an initial intravenous (IV) infusion of JX-594 on Day 1. This is followed by intratumoral (IT) injections of JX-594 directly into viable liver tumors under imaging guidance on Day 8, Day 22, and Weeks 6, 12, and 18. These patients will also receive BSC, but active anti-cancer treatments are strictly prohibited. In contrast, patients in the control arm receive only Best Supportive Care (e.g., hydration, nutrition, pain management) at the treating physician's discretion without any study drug injections. Experimental or active anti-cancer therapies are not permitted in the control arm.
The primary objective of this study is to compare the Overall Survival (OS) between the two treatment arms. Secondary objectives include evaluating Time-to-Tumor Progression (TTP) and objective response rate based on mRECIST criteria for HCC. The study also evaluates Time-to-Symptomatic Progression (TSP), which is defined by changes in the FACT Hepatobiliary Symptom Index (FHSI-8) questionnaire and ECOG performance status. Additionally, the study assesses changes in Quality of Life (QoL) measured by EORTC and FACT-Hep questionnaires. Finally, overall safety and tolerability are closely monitored through the incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) graded according to NCI CTCAE v4.03, along with clinical laboratory evaluations.
Categories
Completion Date
Completion Date Type
Actual
Conditions
HEPATOCELLULAR CARCINOMA
LIVER CANCER
HCC
Eligibility Criteria
KEY Inclusion Criteria:
* Diagnosis of primary HCC by tissue biopsy (histological/cytological diagnosis), or clinical diagnosis
* Previously treated with sorafenib for ≥ 14 days and has discontinued sorafenib treatment at least 14 days prior to randomization due to either intolerance or radiographic progression NOTE: Sorafenib is NOT required to be the most recent treatment received for HCC
* ECOG performance status 0, 1 or 2
* Child-Pugh Class A; or Child-Pugh Class B7 without clinically significant ascites
* Hematocrit ≥30% or Hemoglobin ≥10 g/dL
* Tumor status: Measurable viable tumor in the liver and injectable under imaging-guidance; At least one tumor in the liver that has not received prior local-regional treatment OR that has exhibited \>25% growth in viable tumor size since prior local-regional treatment.
KEY Exclusion Criteria:
* Received sorafenib within 14 days prior to randomization
* Received systemic anti-cancer therapy other than sorafenib within 28 days of randomization
* Prior treatment with JX-594
* Platelet count \< 50,000 PLT/ mm3
* Total white blood cell count \< 2,000 cells/mm3
* Prior or planned organ transplant
* Known significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication
* Severe or unstable cardiac disease
* Viable CNS malignancy associated with clinical symptoms
* Pregnant or nursing an infant
* History of inflammatory skin condition (e.g., eczema requiring previous treatment, atopic dermatitis)
* Diagnosis of primary HCC by tissue biopsy (histological/cytological diagnosis), or clinical diagnosis
* Previously treated with sorafenib for ≥ 14 days and has discontinued sorafenib treatment at least 14 days prior to randomization due to either intolerance or radiographic progression NOTE: Sorafenib is NOT required to be the most recent treatment received for HCC
* ECOG performance status 0, 1 or 2
* Child-Pugh Class A; or Child-Pugh Class B7 without clinically significant ascites
* Hematocrit ≥30% or Hemoglobin ≥10 g/dL
* Tumor status: Measurable viable tumor in the liver and injectable under imaging-guidance; At least one tumor in the liver that has not received prior local-regional treatment OR that has exhibited \>25% growth in viable tumor size since prior local-regional treatment.
KEY Exclusion Criteria:
* Received sorafenib within 14 days prior to randomization
* Received systemic anti-cancer therapy other than sorafenib within 28 days of randomization
* Prior treatment with JX-594
* Platelet count \< 50,000 PLT/ mm3
* Total white blood cell count \< 2,000 cells/mm3
* Prior or planned organ transplant
* Known significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication
* Severe or unstable cardiac disease
* Viable CNS malignancy associated with clinical symptoms
* Pregnant or nursing an infant
* History of inflammatory skin condition (e.g., eczema requiring previous treatment, atopic dermatitis)
Inclusion Criteria
Inclusion Criteria:
* Diagnosis of primary HCC by tissue biopsy (histological/cytological diagnosis), or clinical diagnosis
* Previously treated with sorafenib for ≥ 14 days and has discontinued sorafenib treatment at least 14 days prior to randomization due to either intolerance or radiographic progression NOTE: Sorafenib is NOT required to be the most recent treatment received for HCC
* ECOG performance status 0, 1 or 2
* Child-Pugh Class A; or Child-Pugh Class B7 without clinically significant ascites
* Hematocrit ≥30% or Hemoglobin ≥10 g/dL
* Tumor status: Measurable viable tumor in the liver and injectable under imaging-guidance; At least one tumor in the liver that has not received prior local-regional treatment OR that has exhibited \>25% growth in viable tumor size since prior local-regional treatment.
* Diagnosis of primary HCC by tissue biopsy (histological/cytological diagnosis), or clinical diagnosis
* Previously treated with sorafenib for ≥ 14 days and has discontinued sorafenib treatment at least 14 days prior to randomization due to either intolerance or radiographic progression NOTE: Sorafenib is NOT required to be the most recent treatment received for HCC
* ECOG performance status 0, 1 or 2
* Child-Pugh Class A; or Child-Pugh Class B7 without clinically significant ascites
* Hematocrit ≥30% or Hemoglobin ≥10 g/dL
* Tumor status: Measurable viable tumor in the liver and injectable under imaging-guidance; At least one tumor in the liver that has not received prior local-regional treatment OR that has exhibited \>25% growth in viable tumor size since prior local-regional treatment.
Gender
All
Gender Based
false
Keywords
liver cancer
liver tumor
hepatocellular cancer
Jennerex
HCC
Advanced HCC
sorafenib
sorafenib failure
sorafenib intolerant
Nexavar
Nexavar failure
JX594
oncolytic virus
viral therapy
JX
Biotherapeutics
vaccinia
HEP018
traverse
biologic
Pexa-Vec
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01387555
Org Class
Industry
Org Full Name
SillaJen, Inc.
Org Study Id
JX594-HEP018
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 2b Randomized Trial of JX-594 (Vaccinia GM-CSF / TK-deactivated Virus) Plus Best Supportive Care Versus Best Supportive Care in Patients With Advanced Hepatocellular Carcinoma Who Have Failed Sorafenib Treatment
Primary Outcomes
Outcome Description
Determine overall survival for patients receiving JX-594 plus best supportive care (Arm A) compared with those patients receiving best supportive care (Arm B) in patients with advanced hepatocellular carcinoma (HCC) who have failed sorafenib treatment.
Outcome Measure
Survival
Outcome Time Frame
From randomization until death from any cause, assessed up to 21 months.
Secondary Outcomes
Outcome Description
Determine time-to-tumor-progression (TTP) for JX-594 + BSC compared with BSC alone based on mRECIST for HCC. Progression is defined as 2 consecutive time points with increases in the sum of the longest diameters (SLD) of viable target tumors of at least 20% for each time point.
Outcome Time Frame
CT scan every six weeks until progression or death, assessed up to 21 months
Outcome Measure
Time to Tumor Progression
Outcome Description
Change in Quality of Life (QoL) over time based on the physical well-being and additional concerns domains of the Functional Assessment of Cancer Therapy - Hepatobiliary (FACT-Hep) Questionnaire. The FACT-Hep measures health-related quality of life in patients with hepatobiliary cancer. The item scores from these specific subscales are summed to compute a combined score. The combined score ranges from 0 to 100. Higher scores represent a better quality of life and a better outcome.
Outcome Time Frame
Baseline to Visit 8 (Week 6 ) and Visit 11 (Week 12)
Outcome Measure
Mean Percent Change From Baseline in Quality of Life (FACT-Hep Score)
Outcome Description
The overall disease control rate is defined as the percentage of patients achieving a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) for Hepatocellular Carcinoma (HCC). Per mRECIST for HCC, CR is the disappearance of any intratumoral arterial enhancement in all target lesions; PR is a \>=30% decrease in the sum of the longest diameters (SLD) of viable target lesions; and SD is disease that does not qualify for either PR or progressive disease. Best response over all time points after Baseline was used.
Outcome Time Frame
CT scan every 6 weeks until progression or death, assessed up to 21 months
Outcome Measure
Overall Disease Control Rate (Tumor Response)
Outcome Description
Safety will be assessed by the number of adverse events (AEs) and serious adverse events (SAEs)
Outcome Time Frame
Up to 28 days after the last dose of study drug, assessed up to 14 months.
Outcome Measure
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Outcome Description
Symptomatic progression is defined as a decrease of 4 points or more from Baseline in the FHSI-8 questionnaire (that was confirmed 3 weeks later), or a decrease in ECOG performance status to 4, or death.
Outcome Time Frame
From randomization until symptomatic progression or death, assessed up to 21 months
Outcome Measure
Time-to-symptomatic-progression
See Also Links
Url
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Andreas Kaubisch
Investigator Email
akaubisc@montefiore.org
Investigator Phone
718-920-7100
Categories Mesh Debug
Cancer --- CARCINOMA
Cancer --- NEOPLASMS
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Digestive System --- DIGESTIVE SYSTEM DISEASES
Liver --- DIGESTIVE SYSTEM DISEASES
Digestive System --- LIVER DISEASES
Liver --- LIVER DISEASES
COVID-19 --- VIRUS DISEASES
Hepatitis --- VIRUS DISEASES
Infectious Disease --- VIRUS DISEASES
COVID-19 --- INFECTIONS
Infectious Disease --- INFECTIONS
MeSH Terms
CARCINOMA, HEPATOCELLULAR
LIVER NEOPLASMS
VACCINIA
OCULOCEREBRAL HYPOPIGMENTATION SYNDROME TYPE PREUS
ADENOCARCINOMA
CARCINOMA
NEOPLASMS, GLANDULAR AND EPITHELIAL
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
DIGESTIVE SYSTEM NEOPLASMS
NEOPLASMS BY SITE
DIGESTIVE SYSTEM DISEASES
LIVER DISEASES
POXVIRIDAE INFECTIONS
DNA VIRUS INFECTIONS
VIRUS DISEASES
INFECTIONS